END-ON TEMPLATE METHOD FOR META C-H ACTIVATION

1. WELCOME

2. PRESENTED BY
ANU.S
PHARMACEUTICAL CHEMISTRY
END-ON TEMPLATE METHOD
FOR META C-H ACTIVATION

3. CONTENTS
INTRODUCTION
CATALYTIC CYCLE FOR META C-H
ACTIVATION OLEFINATION
APPLICATIONS OF END-ON TEMPLATE
METHOD IN CHEMISTRY
DRUG TARGETS THAT BENEFIT FROM
META C-H ACTIVATION
CONCLUSION
REFERENCES

4. INTRODUCTION
 C-H activation
 Involves replacement of strong terminal C-H
bonds with a functional group.

5.  Electrophilic aromatic substitution reaction is the
basis for many of modification reactions in
pharmaceutical compounds.
 Due to the presence of an electron donating
group in the aromatic system, the substitution at
the meta position is difficult.
 End-on template method is a novel approach of
substitution of functional groups at meta C-H
position.

6.  It is a novel meta C-H activation approach in
modification of drug molecule.
 Modifying organic molecule that significantly
helps in developing new pharmaceuticals and
improving old ones.

7.  Method involves
 Temporary attachment of a helper molecule to one
carbon atom, that extends the nearest carbon atom
and mediates the addition of a functional group.
 Metal catalyst like palladium helps in the process.

8. Template
H
metal catalyst
Template
H M
Cyclophene like pretransition state
Functionalization
Template
Functional group

9. CATALYTIC CYCLE FOR META C-H ACTIVATION
OLEFINATION

10.  Example for end-on template reaction

11. Meta selective C-H methylation
2,2'-iminobis(4-methoxybenzonitrile)

12.  Advantages of end-on template method
 Easily removable template

13.  APPLICATIONS OF END-ON TEMPLATE METHOD
IN CHEMISTRY
 Used to modify compounds like
 Tetrahydro quinolines
 Benzoxazines
 Aniline
 Benzylamines
 2-phenyl pyrazolidines
 2-phenylpiperidines etc.

14.  Overrides intrinsic electronic and steric
bias of molecules
 β-hydride elimination for 1o and 2o alkyls
 Activates distal C-H bonds

15. DRUG TARGETS THAT BENEFIT FROM META C-H
ACTIVATION
ANTI HYPERLIPIDEMIC DRUGS

16.  GABA AGONIST

17. ANTI CANCER DRUG

18. ANTI HYPERTENSIVE DRUG

19. CONCLUSION
 End-on template method is applied directly to
many medicinally relevant compounds
 Helps easier modification of existing organic
compounds by attaching biologically active
functional groups to a drug molecule.

20. REFERENCES
 Wan, L.; Dastbaravardeh, N.; Li, G.; Yu, J. -Q. J. Cross-
coupling of remote meta-C-H bonds directed by a U-shaped
template, Journal of the American Chemical Society, 2013 Dec
4;135(48):18056-9
 Ri-Yuan Tang,Gang Li & Jin-Quan Yu, Conformation-induced
remote meta-C–H activation of amines, Nature 507, 215–
220 (13 March 2014)
 Daugulis O, Do HQ, Shabashov D, Palladium- and copper-
catalyzed arylation of carbon-hydrogen bonds, Accounds of
Chemical Research, 2009 Aug 18;42(8):1074-86

21. • Chen X, Engle KM, Wang DH, Yu JQ , Palladium(II)-catalyzed
C-H activation/C-C cross-coupling reactions: versatility and
practicality, Angewandte Chemie International Edition,
2009;48(28):5094-115
•Ackermann L, Vicente R, Kapdi AR, Transition-metal-catalyzed
direct arylation of (hetero)arenes by C-H bond cleavage,
Angewandte Chemie International Edition, 2009;48(52):9792-826
All information were collected from various
sources, only for educational purpose…….

22. THANK
YOU….